Abstract
Two new 99mTc-labeled neurotensin(8-13) analogues containing the retro-N(alpha)-carboxymethyl-histidine ((N(alpha)His)Ac) chelator were synthesized as potential radiopharmaceuticals for visualization of pancreatic carcinoma. To improve the pharmacokinetic properties, (N(alpha)His)Ac-Arg-NMeArg-Pro-Tyr-Tle-Leu (NT-XII), which is metabolically stabilized at two positions, was further modified. Shikimic acid (3,4,5-trihydroxy-1-cyclohexene-1-carboxylic acid) was introduced to obtain a more hydrophilic peptide (NT-XVIII), or Tyr11 was replaced by 2,6-dimethyltyrosine (Dmt) resulting in a triple-stabilized NT(8-13) analogue (NT-XIX). The latter has the best biodistribution profile.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Chelating Agents / chemical synthesis*
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Chelating Agents / chemistry
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Chelating Agents / pharmacokinetics
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Drug Stability
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Humans
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In Vitro Techniques
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Mice
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Mice, Nude
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Neoplasm Transplantation
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Neurotensin / chemical synthesis*
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Neurotensin / chemistry
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Neurotensin / pharmacokinetics
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Oligopeptides / chemical synthesis*
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Oligopeptides / chemistry
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Oligopeptides / pharmacokinetics
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Organotechnetium Compounds / chemical synthesis*
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Organotechnetium Compounds / chemistry
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Organotechnetium Compounds / pharmacokinetics
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Peptide Fragments / chemical synthesis*
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Peptide Fragments / chemistry
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Peptide Fragments / pharmacokinetics
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Plasma
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Radiopharmaceuticals / chemical synthesis*
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Radiopharmaceuticals / chemistry
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Radiopharmaceuticals / pharmacokinetics
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Shikimic Acid / chemistry
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Structure-Activity Relationship
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Tissue Distribution
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Transplantation, Heterologous
Substances
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(99mTc(CO)(3))-(NalphaHis)acetyl-arginyl-N-methylarginyl-prolyl-2',6'-dimethyltyrosyl-alpha-tert-butylglycyl-leucine
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Chelating Agents
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Oligopeptides
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Organotechnetium Compounds
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Peptide Fragments
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Radiopharmaceuticals
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Shikimic Acid
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Neurotensin
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neurotensin (8-13)